Background Lupus nephritis (LN) is inflammation of the kidneys and is regarded as the most severe manifestation of systemic lupus erythematosus (SLE). Inflammation may lead to excessive production of reactive oxygen species (ROS), which can induce oxidative stress. Plasma-free thiols (R-SH) reliably reflect systemic oxidative stress, since they are readily oxidized by reactive species. Measuring the critical components of redox signaling could be a good way to identify patients with high-level oxidative stress. Free Thiols and soluble receptor for advanced glycation end-products (sRAGE) are critical compounds that may act as potential biomarkers.

Aim The aim of the study was to analyze whether levels of free thiols and sRAGE could be used as a marker of renal disease activity in the long-term follow-up of LN patients. Moreover, associations between oxidative stress biomarkers and clinical and biochemical characteristics were investigated.

Methods Forty SLE patients with quiescent disease (Q-SLE) without renal involvement, who met the American College of Rheumatology (ACR) classification criteria for SLE and 23 healthy controls (HC) were included. Also 23 patients with proliferative LN diagnosed based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, who previously participated in Dutch Lupus Nephritis studies¹ with 36 months follow up were included. Plasma-free thiols levels were measured in SLE, LN patients and HC as previously described.² sRAGE levels were measured by ELISA. In addition, the assessment of disease activity was performed using SLEDAI calculation for each patient. The changes in plasma-free thiols and sRAGE levels longitudinally were compared to clinical and biochemical markers using generalized estimating equations (GEE).

Results Thiols levels were significantly lower in active LN (at baseline) and Q-SLE patients compared to HC (Figure1 A). There was no significant difference in sRAGE levels between the groups (Figure 1 B). The median of changes in plasma-free thiols and sRAGE levels during the 36-month follow-up are shown in figure 2. In the univariate GEE model (table 1), changes of plasma-free thiols were negatively correlated with SLEDAI (p <0.001). Changes of sRAGE were also correlated with SLEDAI (p=0.035). In addition, changes of plasma-free thiols were also correlated with creatinine levels.

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Abstract PO.5.111 Figure 1

Active LN is associated with lowered plasma-free thiols levels. A) Plasma-free thiols levels in active LN patient‘s at baseline are significantly decreased compared to quiescent SLE patients and HC. B) sRAGE levels are not different between the groups. A-LN: active lupus nephritis, Q-SLE: Quiescent systemic lupus erythematosus, CTRL: healthy control

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Abstract PO.5.111 Figure 2

(A) Median plasma-free thiols levels during 36 months follow-up in LN patient‘s; (B) sRAGE levels during 36 montsh follow-up in LN patient‘s

Conclusions Plasma-free thiols levels are significantly reduced in patients with SLE and LN at baseline compared to HC. In follow-up of LN patients, free thiols levels are significantly negatively correlated to SLEDAI. These results suggest that free-thiols could be a potential additional redox signaling marker to evaluate the activity of LN.

Reference

1. Arends S, et al. Long-term follow-up of a randomized controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis, Ann Rheum Dis.

2. Bourgonje AR, et al. Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease, Antioxidants (Basel).